Pantothenate and CoA biosynthesis
Coenzyme A (CoA) is an important cofactor (acyl-chain carrier) for many cellular functions including the citrate cycle and fatty acid biosynthesis and metabolism. Vitamin B5, also known as pantothenate is the precursor for CoA biosynthesis. Pantothenate synthesis takes place in plants, fungi and some bacteria, whereas animals salvage pantothenate from diet and CoA biosynthesis from pantothenate is present in most organisms. Plasmodium falciparum utilises pantothenate from host and converts it to CoA (CoA biosynthesis). In contrast, the Coccidians Toxoplasma gondii and Neospora caninum possess the four enzymes required for the generation of pantothenate from the branched chain amino acid valine. Except dephospho-CoA kinase (2.7.1.24), all other enzymes involved in the downstream conversion of pantothenate to CoA are present. Dephospho-CoA kinase, an enzyme present in P. falciparum is missing in T. gondii and N. caninum gene models. It has previously been suggested that T. gondii pantothene-phosphate adenyl-transferase enzyme is similar to the mammalian bifunctional enzyme and possesses both pantothene-phosphate adenyl-transferase (2.7.7.3) and dephospho-CoA kinase activities, whereas P. falciparum and Cryptosporidium species have two separate enzymes [1]. The only known protein domain present in T. gondii and N. caninum 2.7.7.3 enzymes (TGME49_030990 & NCLIV_031360) is nucleotidyl-transferase, the same as in the P. falciparum enzyme, whereas mammalian enzyme possesses dephospho-CoA kinase domain as well. This suggests that Toxoplasma and Neospora enzymes are mono functional.
Enzyme | EC Number | Gene id |
---|---|---|
Bifunctional 2-dehydropantoate 2-reductase/3-methyl-2-oxobutanoate hydroxymethyltransferase | 1.1.1.169; 2.1.2.11 | NCLIV_029910 |
Branched-chain-amino-acid-transaminase | 2.6.1.42 | NCLIV_006760 |
Branched-chain-amino-acid-transaminase | 2.6.1.42 | NCLIV_023450 |
Dephospho-CoA kinase | 2.7.1.24 | Missing in annotation |
Pantothenate kinase | 2.7.1.33 | NCLIV_049910 |
Pantothenate kinase | 2.7.1.33 | NCLIV_060530 |
Pantetheine-phosphate adenylyltransferase | 2.7.7.3 | NCLIV_031360 |
Holo-[acyl-carrier-protein] synthase | 2.7.8.7 | NCLIV_021530 |
Holo-[acyl-carrier-protein] synthase | 2.7.8.7 | NCLIV_051620 |
Phosphopantothenoylcysteine decarboxylase | 4.1.1.36 | NCLIV_017870 |
Pantoate-beta-alanine ligase | 6.3.2.1 | NCLIV_039640 |
Phosphopantothenate-cysteine ligase | 6.3.2.5 | NCLIV_010940 |
Apo-[acyl-carrier protein] | none | NCLIV_023990 |
Apo-[acyl-carrier protein] | none | NCLIV_036350 |
Sources and fates of metabolites
Substrate | Source pathways | Product | Fate pathways |
---|---|---|---|
L-valine | Host | CoA | Tricarboxylic acid (TCA) cycle |
2-oxoglutarate | Pyruvate metabolism, Tricarboxylic acid (TCA) cycle | Glutamate | Glutamate metabolism |
Methylene-THF | Folate biosynthesis | THF | Folate biosynthesis |
beta-alanine | Host | ||
Cysteine | Glycine, serine and cysteine metabolism |
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